1. Field of the Invention
The present invention relates to a method for the treatment of disorders of the vascular and pulmonary systems, such as vascular aging and arteriosclerosis and disorders of the lungs associated with smoking.
2. Description of the Prior Art
The normal vascular system of mammals, especially humans, includes all of the organs, such as the heart and the arteries, involved in blood transport and circulation. Two major disorders affect the vascular system in animals: arteriosclerosis and aging. Arteriosclerosis, a generic term for the thickening and hardening of the arterial wall, is responsible for the majority of deaths in the United States and most Westernized societies. There are various types of arteriosclerosis such as atherosclerosis, focal calcification, and arteriolosclerosis. The changes associared with arteriosclerosis (of the various types) and aging are partly overlapping. (See for example Harrison's "Principles of Internal Medicine," 9th Edition, pp. 156-1166.)
The normal artery wall consists of rhree reasonably well defined layers: the intima, the media and the adventitia. The intima is a layer of endothelial cells lining the lumen of all arteries. The endothelial cells are attached to each other by a series of junctional complexes and also are attached to an underlying meshwork of loose connective tissue, the basal lamina. The lining endothelial cells form a barrier that controls the entry of substances from the blood into the arterial wall. The media consists of smooth muscle cells arranged in either single layers or multiple layers. The outermost layer of the artery is the advenritia which is delimited by the external elastic lamina. This external coat consists of a loose interwoven mixture of thick bundles of collagen, elastic fibers of varying size and a mixture of smooth muscle cells and fibroblasts.
Maintenance of the endothelial cell lining is critical. Endothelial cell turnover occurs at a slow rate but may accelerate in focal areas by changing patterns of flow along the vessel wall. Intact endothelial cells function to prevent clotting partly by elaboration of prostacyclin that inhibits platelet function, thereby enhancing unimpeded flow of blood. When the lining is damaged, however, platelets adhere to it in part as the result of production of a different class of prostaglandins, the thromboxanes, and form a clot. The ability of the arterial wall to maintain the integrity of its endothelium, prevent platelet aggregation and insure the nutrition of its middle portion may be the critical determinants of the arteriosclerotic process.
The major change that occurs with normal aging in the arterial wall is a slow symmetrical increase in the thickness of the intima. This results from an accumulation of small muscle cells. In the nondiseased artery wall the lipid content, mainly cholesterol ester and phospholipid, also progressively increases with age. While most of the phospholipid in the normal artery wall appears to be derived from in situ synthesis, the cholesterol ester that accumulates with aging appears to be derived from plasma, since it contains principally linoleic acid, the major plasma cholesterol ester of fatty acid. As the normal artery ages, smooth muscle cells and connective tissue accumulate in the intima, leading to progressive thickening of the layer coupled with progressive accumulation of fatty acid, resulting in a gradual increase in the rigidity of the vessels. The larger arteries may become dilated, elongated and porous and aneurysms may form in areas of encroaching degenerating arteriosclerotic plaque.
By far, the leading cause of death in the United States both above and below age 65 is atherosclerosis, the atheromatous form of arteriosclerosis. The lesions are commonly classifed as fatty streaks, fibrous plaques and complicated lesions. The fatty streaks are characterized by an accumulation of lipid-filled smooth muscle cells and fibrous tissue in focal areas of the intima, and are stained distinctively by fat soluble dyes. The lipid is mainly cholesterol oleate. Fibrous plaques are elevated areas of intima thickening and will present the most characteristic lesion of advancing arteriosclerosis. They appear in the abdominal aorta, coronary arteries and carotid arteries in the third decade and increase progressively with age. Complicated lesions are calcified fibrous plaques containing various degrees of necrosis, thrombosis and ulceration.
A number of factors called "risk factors" have been identified in individuals who develop atherosclerosis. The risk factor concept implies that a person with at least one risk factor is more likely to develop a clinical atherosclerotic event and to do so earlier than a person with no risk factors. The presence of multiple risk factors further accelerates atherosclerosis. Among the reversible or partially reversible risk factors are hyperlipidemia (hypercholesterolemia and/or hypertriglyceridemia), hyperglycemia and diabetes, low levels of high density lipoproteins, hypertension, obesity, and cigarette smoking.
As stated in Harrison's, supra (p 1166), although the emergence of clinical consequences of atherosclerosis can be lessened, no convincing instance of regression or interruption of progression of atherosclerosis by removal or reversal of any single or group of risk factors has yet been proved in humans. The trend toward lower smoking, lower cholesterol and fat consumption and towards reduction of overweight and exercise programs has been helpful. Prevention rather than treatment, however, is the goal of public health professionals. An effective program of prophylaxis has not yet been established, although enough is known to guide in both identification and high risk and development of measures to reduce the risk.
Among the risk factors referred to above that mighr be particularly well suited to therapeutic treatment is hyperlipidemia. Although control of factors such as obesity and cigarette consumption depend, to a great degree, on the will and inclination of the individual, if a reasonable method for lowering, e.g., serum cholesterol, low density lipids (LDL) and triglyceride blood stream levels were provided, it would be suitable for treatment of a broad spectrum of individuals.
Because of the widespread distribution of vascular disorders such as arteriosclerosis disorders and the naturally occurring aging of the vascuIar system and its accompanying problems, a need exists for an effective method for both preventing and possibly treating these disorders.
If a natural food product, such as milk for example, could be obtained having anti-arteriosclerotic and aging effects it would be an easily administerable, readily available, safe therapeutic composition.
Another major system of mammals, especially humans, which is characterized by the progressive degeneration of the cells of the organs constituting that system, is the pulmonary system, and in particular, the lungs and associated bronchii and alveoli. Like arteriosclerosis and vascular aging, certain pulmonary disorders, including a general breakdown of the pulmonary system, short windedness and a decrease in the efficiency of the respiration is associated with and due to environmental irritants and pollutants, such as those contained in cigarette smoke.
It is known that prolonged smoking induces the accumulation of deposits of carbon and other substances on and in the lungs, which destroy the respiratory function of the associated area. Similarly, smoking, and/or the presence of these deposits substantially increases the number of neutrophilis and lymphocytes present in mammalian lungs, both types of cells producing substances that are injurious to lung tissue.
As with arteriosclerosis, there has been some containment or alleviation of the disorders associated with smoking due to a reduction in the frequency of smoking in most age groups. However, in certain segments of the population, most notably teen age and young women, smoking has increased, multiplying the frequency of occurrence of disorders associated with smoking both in the current population and importantly in the foreseeable future.
As with cardiovascular diseases, treatment based on avoidance of pollutants such as smoking will have varying success, depending on the individual. But, if a method for reducing the amount of deposited matter could be found, such as stimulation of lung macrophage activity, a treatment of benefit to most individuals could be developed.
As with arteriosclerotic and vascular diseases in general, if a natural food product, such as milk for example could be obtained having a sparing effect on lungs exposed to smoke and the associated disorders, it would be an easily administerable, readily available, safe therapeutic composition.
It has been known in the prior art to produce milks having a variety of therapeutic effects. Beck, for example, has disclosed a milk containing antibody to Streptococcus mutans which has dental caries inhibiting effects (Beck, U.S. Pat. No. 4,324,782). The milk is obtained by immunizing a cow with S. mutans antigen in two stages and obraining the therapeutic milk therefrom. Beck has also described a milk having anti-arthritic properties (copending U.S. Ser. No. 875,140 filed Feb. 6, 1978), and has described and patented a milk having anti-inflammatory properties (U.S. Pat. No. 4,284,623). Heinbach, U.S. Pat. No. 3,128,230, has described milk containing globulins of .alpha.,.beta.,.gamma. components, by innoculating a cow with anti9enic mixtures. Petersen (U.S. Pat. No. 3,376,198 and Canadian Pat. No. 587,849), Holm, U.S. application (published) Ser. No. 628,987 and Tunnak et al. (British Pat. No. 1,211,876) have also described antibody-containing milks.
None of the aforementioned references, however, disclose or suggest milk having antiarteriosclerotic or vascular anti aging properties or a sparing affect on lungs exposed to smoke.